Despite recent innovative progresses in the therapy of heart diseases, no firm therapeutic system has been established yet for severe heart failure. A common method for treating heart failure is that of medical therapy by means of β-blockers or an ACE inhibitor. Heart failure too severe to be effectively cured by such therapy is treated by replacement therapy with an auxiliary artificial heart or by heart transplantation, i.e., surgical therapy.
There are various causes for severe heart failure such that surgical therapy is needed. They include proceeded valvular disease, hyper myocardial ischemia, acute myocardial infarction and its complications, acute myocarditis, chronic cardiac failure due to ischemic myocarditis (ICM), dilated cardiomyopathy (DCM) or the like, and its acute oxacerbation.
Various techniques are applied to the foregoing diseases depending on their cause and severity. They include valvuloplasty, replacement, coronary artery bypass, left ventricular plasty, and mechanically assisted circulation.
It has been thought that the only way for effective treatment of cardiac failure resulting from the severely decreased function of left ventricle due to ICM and DCM is by replacement therapy involving heart transplantation and an artificial heart. However, replacement therapy for severe cardiac failure patients has many problems including a constant deficiency in the number of donors, the necessity for continuous immunosuppression, and various other complications. Therefore, it would be difficult to assert that replacement therapy is universally acceptable for treating severe cardiac failure.
In order to cope with the harsh situation surrounding heart transplantation, attempts were made for a short time to replace the foregoing surgical therapy by a new one such as the Batista operation procedure. This procedure attracted great attention as a substitute for heart transplantation. However, its limitations have recently been identified, and attempts are being made to improve this surgical procedure and its adequate application.
On the other hand, recently, the significance of the need for developing regenerative medicine as a new means for treating severe heart failure has been recognized.
Severe myocardial infarction or the like leads to incompetence of myocardial cells, which can further progress to the proliferation of fibroblasts and fibrosis of stroma, and eventually to heart failure. The progress of heart failure damages myocardial cells and leads to apotosis. As a result, myocardial cells, which undergo minimal cell division, decrease in number, thereby rendering the cardiac function even more incompetent.
It is considered that an effective way to reestablish healthy cardiac function for patients that have experienced severe heart failure is by cell transplantation. In fact, the transplantation of autoskeletal myoblasts has reached the stage of clinical application.
One example of the recent advancement of this technology is the production of three-dimensional cell cultures (for treating the heart) containing cells derived from any part of an adult other than their cardiac muscle, which has been realized by tissue engineering that employs temperature-responsive culture dishes. Such cell cultures and the method for production thereof have been disclosed Japanese Patent Laid-open No. 2007-528755.